Desmoplastic Small Round Cell Tumor: Imaging Pattern of Disease at Presentation.
The purpose of this study is to evaluate the clinical, pathologic, and multimodality cross-sectional imaging features of a cohort of 94 patients with desmoplastic small round cell tumor (DSRCT). This retrospective study of 94 patients with pathologically verified DSRCT was conducted at a tertiary cancer center between 2001 and 2013. Epidemiologic, clinical, pathologic, and imaging findings were recorded. Tumor size, location, and shape and the distribution pattern of metastases at presentation were analyzed. DSRCT most often occurred in young patients (median age, 21.5 years; range, 5-53 years), showing a marked predominance in male patients (86 male patients vs eight female patients). Eighty nine-patients (95%) were white (defined in this study as white or Hispanic), four were African American, and one was of Asian descent. Most patients had symptoms, with abdominal pain noted as the most common symptom. At initial presentation, 85 patients (90%) had multifocal disease, nodular disease, diffuse omental and peritoneal disease, or a combination of these conditions. Thirty-eight patients (40%) had diaphragmatic involvement. Thirty-two patients (34%) had liver metastases, and 49 patients (52%) had retroperitoneal involvement in the form of implants, tumoral extension, or nodal involvement. With regard to thoracic findings, 33 patients (35%) had nodal disease, 17 (18%) had pleural effusions, and only two (2%) had lung metastases at presentation. Twelve patients (13%) had calcified lesions. DSRCT is a rare, multifocal peritoneal malignancy with frequently disseminated abdominal disease at presentation. In the abdomen, disease most commonly involves the omentum and peritoneum, followed by the retroperitoneum. The liver is the most common solid visceral metastatic site. A substantial number of patients have diaphragmatic involvement. In the thorax, nodal and pleural involvement is more common than lung involvement.


Effectiveness of bisphosphonates on bone mineral density in osteopenic postmenopausal women: A systematic review and network meta-analysis of randomized controlled trials.
Various bisphosphonate agents have been proven to be effective in preventing bone loss and fracture in osteopenic postmenopausal women. This study was designed to compare the effectiveness of various BPs on preventing the loss of bone mineral density (BMD) for postmenopausal women with osteopenia. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were screened up to identify randomized controlled trails comparing effectiveness of BPs or placebo on the BMD of postmenopausal women with osteopenia. Network meta-analysis and standard pair-wise meta-analyses were performed. The main outcomes include the percentage changes of 6-, 12-, 24-, and 36-month BMD at lumbar, total hip and femoral neck, and frequencies of new fractures and severe adverse events. Fourteen randomized controlled trials were eligible, involving 11,540 participants. No significant difference was presented among the available interventions for the 6-month BMD at 3 different sites, but the magnitudes of differences among the treatment regimens became gradually increased along with the extending of follow-up periods. Daily aledronate of more than 5 mg provided the maximal percentage increase on BMD of femoral neck and lumbar spine, while zoledronate provided maximal change on BMD of total hip, at different follow-up periods. This network meta-analysis also demonstrated similar frequencies of new clinical fractures and severe adverse events among different interventions. A ranking spectrum depicting the effectiveness on BMD percentage change following interventions with different bisphosphonate regimens was provided. Generally, regimens with zoledronate and aledronate were found to be the most effective interventions in the 3 sites at different end points.


High-Sensitivity Cardiac Troponin T in Patients with Acute Myocardial Infarction in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
In clinical work, patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) often have high-sensitivity cardiac troponin T (hs-cTnT) levels that surpass the 99th percentile of the normal reference population, a cutoff used to screen patients for acute myocardial infarction (AMI). However, a large proportion of these patients prove not to have AMI and are frequently misdiagnosed and overtreated. We analyzed whether the cutoff value of hs-cTnT for diagnosing AMI in AECOPD patients should be adjusted. This was a prospective study of 873 consecutive patients with AECOPD who presented at the emergency department of West China Hospital of Sichuan University from January 2010 to December 2013. Conventional cardiac troponin (cTnT) was measured in patients' blood samples taken at presentation, and values were compared with their final diagnoses. Among patients with a final diagnosis other than AMI, 64.64% had a plasma hs-cTnT concentration above the 99th percentile of a normal reference population (14 ng/L). The median level of hs-cTnT in AECOPD patients without AMI was 16 ng/L. The area under the receiver-operating characteristic curve (AUC) of hs-cTnT for diagnosis of AMI was 0.92 (0.85 - 0.99, p < 0.001) with a cutoff value of 60.5 ng/L. The baseline levels of hs-cTnT were relatively high in AECOPD patients, and the optimal cutoff value of hs-cTnT for AMI diagnosis (60.5 ng/L) was also higher than that for non-AECOPD patients.


Comparison of the effects of Ham'sF10 and αMEM in combination with FBS or BSA in vitrification/warming solution on quality and viability of sheep ovarian follicles.
The aim of this study was to evaluate the effects of the two types of media, namely minimum essential medium (αMEM) and Ham'sF10, supplemented with foetal bovine serum (FBS) or bovine serum albumin (BSA) in vitrification/warming solution on the quality and viability of sheep ovarian follicles. Vitrification method was applied for cryopreservation of sheep ovarian cortex using Ham'sF10 and αMEM supplemented with either BSA or FBS. There were five groups: Fresh, Ham'sF10+ BSA, Ham'sF10+ FBS, αMEM + BSA and αMEM + FBS. Samples were cultured for two weeks after warming. Viability and morphology of follicles and DNA fragmentation in follicles and in tissue stroma cells were analysed before vitrification/warming and following one and two weeks of culture. The Ham'sF10+ FBS and Ham'sF10+ BSA groups showed a significant decrease in follicular viability after one week of culture (p < .05 vs. Fresh). Following two weeks of culture, all groups revealed a considerable fall in the number of viable follicles (p < .05 vs. Fresh). There was an increase in DNA fragmentation of connective tissue cells but not in the follicles (p < .05). Our results showed the better application of αMEM supplemented with BSA as a vitrification solution in improvement of cryopreservation effects and maintenance of follicular survival.


A look at a Hispanic and African American population in an urban prenatal diagnostic center: referral reasons, amniocentesis acceptance, and abnormalities detected.
To describe the Hispanic and African-American population referred to our inner city Los Angeles Prenatal Diagnostic Center. To evaluate trends in referral reasons, amniocentesis acceptance, and to assess the number and types of fetal abnormalities found from 1995 to 2001. A retrospective study using the data from 3085 daily log entries on patients referred for prenatal counseling. The data included race, age, referral reason, amniocentesis decision and results, and fetal abnormalities. The population was 76% Hispanic and 22% African American. Most referrals were for advanced maternal age (42%) and maternal serum screening (28%). The overall amniocentesis acceptance rate was 52%; advanced maternal age amniocentesis acceptance rate was 46%, and maternal serum screen positive amniocentesis acceptance rate was significantly higher at 64%. There was a significant difference between the overall amniocentesis acceptance rate for Hispanics (48%) and African Americans (63%). There was also a significant downward trend in amniocentesis acceptance between 1995 (63%) and 2001 (39%). Amniocentesis acceptance was significantly greater among patients who were < 35 years of age (65%) than those who were older (47%). An incidence of 7% abnormalities was detected by ultrasound and amniocentesis. Acceptance of amniocentesis in the Hispanic and African American population in our prenatal diagnostic center is significantly lower than what has previously been reported in the literature for Caucasians and reported in California statewide prenatal diagnostic center data for non-MS-AFP. There was a significant decline in amniocentesis acceptance from 1995 to 2001. Our incidence of fetal abnormalities was higher than reported in California statewide data.


CHO-S antibody titers >1 gram/liter using flow electroporation-mediated transient gene expression followed by rapid migration to high-yield stable cell lines.
In recent years, researchers have turned to transient gene expression (TGE) as an alternative to CHO stable cell line generation for early-stage antibody development. Despite advances in transfection methods and culture optimization, the majority of CHO-based TGE systems produce insufficient antibody titers for extensive use within biotherapeutic development pipelines. Flow electroporation using the MaxCyte STX Scalable Transfection System is a highly efficient, scalable means of CHO-based TGE for gram-level production of antibodies without the need for specialized expression vectors or genetically engineered CHO cell lines. CHO cell flow electroporation is easily scaled from milligram to multigram quantities without protocol reoptimization while maintaining transfection performance and antibody productivity. In this article, data are presented that demonstrate the reproducibility, scalability, and antibody production capabilities of CHO-based TGE using the MaxCyte STX. Data show optimization of posttransfection parameters such as cell density, media composition, and feed strategy that result in secreted antibody titers >1 g/L and production of multiple grams of antibody within 2 weeks of a single CHO-S cell transfection. In addition, data are presented to demonstrate the application of scalable electroporation for the rapid generation of high-yield stable CHO cell lines to bridge the gap between early- and late-stage antibody development activities.


[Giant Ganglioneuroma of the Spine and Mediastinum].
The case of a 15-year-old girl with a large ganglioneuroma in the mediastinum and spinal canal is presented. The tumour initially manifested as scoliosis. Its diagnosis was made on the basis of CT scanning and magnetic resonance imaging, and confirmed by thoracoscopic mediastinal biopsy. Radical tumour excision was indicated. The first stage involved removal of the tumour from the spinal canal through a posterior approach, and transpedicular fixation of the spinal column with correction of the curve. At the second-stage procedure, the tumour was removed from the pleural cavity and mediastinum through thoracotomy. At two years after surgery, the spondylodesis was completed with autologous bone grafts that healed within 6 months. At 3-year follow-up the patient was with neither clinical findings, nor subjective complains and imaging methods showed no signs of tumour recurrence. ganglioneuroma, scoliosis, correction, thoracotomy, spinal canal, mediastinum.


Patellar tendon re-rupture on the opposite end of the previous site of surgical repair.
We describe a rare case of a patellar tendon "re-rupture" at the opposite end of a previous proximal tendon repair. A 32-year-old male with a history of surgically repaired right proximal patellar tendon rupture presented with an acute non-traumatic right knee pain and instability during sports. Magnetic resonance imaging confirmed a complete rupture of his distal patellar tendon at the tibial tuberosity. The patellar tendon was repaired using two 5.5 mm BioCorkscrews (Arthrex) inserted into the tibial tuberosity; the tendon was stitched with the No. 2 fiberwires using Krackow technique. As the patellar tendon was degenerative, the repair was augmented with a semitendinosus tendon harvested using an open tendon stripper, leaving the distal attachment intact. At 2.6 years followup he had mild anterior knee pain, range of motion 0-130° and was able to squat. MRI scan done at followup revealed good healing of repaired patellar tendon.


Translating knowledge into good practice.
Nurses should value knowledge gained by experience, and pass on such knowledge to new colleagues. Collaboration between nurses and academics is a beneficial method of sharing clinical and academic viewpoints. Reflective groups and journal clubs can help to develop evidence-based practice. Implementing knowledge in practice is a challenge and can be very rewarding for practitioners, as well as improving patient care.


Purification and characterization of an extracellular exochitinase, beta-N-acetylhexosaminidase, from the fungal mycoparasite Stachybotrys elegans.
The mycoparasite Stachybotrys elegans produces two exo- and one endo-acting chitinases when grown on chitin. We purified to homogeneity one of the exo-acting chitinases, beta-N-acetylhexosaminidase and partially characterized its physical and biochemical properties. The native enzyme has a molecular mass of 120 kDa when determined by gel filtration and 68 kDa by sodium dodecyl sulfate - polyacrylamide gel electrophoresis indicating that the native protein probably occurs as a dimer in solution. The purified beta-N-acetylhexosaminidase is most active at pH 5.0 and 40 degrees C and hydrolyzes the p-nitrophenyl-N-acetyl-beta-D-glucosaminide with apparent Km of 84.6 microM. Polyclonal antibodies raised against the 68-kDa beta-N-acetylhexosaminidase (NAG-68) indicated that the antibody is highly specific and recognizes the protein in crude filtrate preparation. This suggests that the protein is a not a proteolytic product of another protein. Western blot analysis showed that the activity of NAG-68 was induced when S. elegans was grown on purified cell wall fragments of its host, Rhizoctonia solani, as well as during antagonistic interaction of the mycoparasite and host when both were grown on synthetic medium with or without supplemental carbon source.


Clinical significance of total gastrectomy for proximal gastric cancer.
The optimal surgical strategy for proximal gastric cancer (PGC) remains controversial. The principal difference between total gastrectomy (TG) and proximal gastrectomy (PG) is whether lymph node (LN) 4d is dissected by radical lymphadenectomy. The subjects were 243 patients with PGC who had undergone TG between 1990 and 2006. The incidences of metastases to individual LNs were assessed. The 5-year disease-specific survival (DSS) was examined in 179 patients who had undergone TG and an additional 37 patients who had undergone PG between 1990 and 2002. When PGC was confined to the muscularis propria (mp), no patient had LN 4d or 8 metastases although these nodes are considered regional LNs, and the 5-year DSS rate did not significantly differ between TG and PG. When the PGC extended beyond the mp, the patients with LN 4d or 8 metastases in N2 disease had very poor outcomes, similar to those with N3 disease. Multivariate analysis revealed that lymph node metastatic density over 40% (ND40) was the strongest independent prognostic factor (p=0.001, HR=6.1). ND40 was significantly associated with LN 4d or 8 metastases in N2 disease (p=0.047). LN 4d or 8 metastasis is equivalent to advanced LN metastasis and the presence of such metastasis indicates a poor prognosis, regardless of LN dissection, thus, PG might therefore be an adequate procedure for LN dissection in patients with PGC.


Elevated amylase creatinine clearance ratio and normal serum amylase levels in chronic relapsing pancreatitis after partial pancreatectomy.
A 29-year-old woman admitted for alcohol detoxification five years after a 90% distal pancreatectomy for chronic pancreatitis had abdominal pain similar to that associated with preoperative pancreatitis. Although her clinical course was consistent with recurrent pancreatitis, the serum amylase level remained normal, but the amylase creatinine clearance ratio became elevated and then returned to normal, paralleling her clinical course. The ACCR may be a useful laboratory method in diagnosing chronic recurrent pancreatitis in patients with decreased functional pancreatic tissue.


A Novel Assay to Measure the Magnitude of the Inducible Viral Reservoir in HIV-infected Individuals.
Quantifying latently infected cells is critical to evaluate the efficacy of therapeutic strategies aimed at reducing the size of the long-lived viral reservoir, but the low frequency of these cells makes this very challenging. We developed TILDA (Tat/rev Induced Limiting Dilution Assay) to measure the frequency of cells with inducible multiply-spliced HIV RNA, as these transcripts are usually absent in latently infected cells but induced upon viral reactivation. TILDA requires less than a million cells, does not require RNA extraction and can be completed in two days. In suppressed individuals on ART, we found the median frequency of latently infected CD4 + T cells as estimated by TILDA to be 24 cells/million, which was 48 times more than the frequency measured by the quantitative viral outgrowth assay, and 6-27 times less than the frequencies of cells harbouring viral DNA measured by PCR-based assays. TILDA measurements strongly correlated with most HIV DNA assays. The size of the latent reservoir measured by TILDA was lower in subjects who initiated ART during the early compared to late stage of infection (p = 0.011). In untreated HIV disease, the frequency of CD4 + cells carrying latent but inducible HIV largely exceeded the frequency of actively producing cells, demonstrating that the majority of infected cells are transcriptionally silent even in the absence of ART. Our results suggest that TILDA is a reproducible and sensitive approach to measure the frequency of productively and latently infected cells in clinical settings. We demonstrate that the latent reservoir represents a substantial fraction of all infected cells prior to ART initiation. In this manuscript, we describe the development of a novel assay that measures the magnitude of the latent HIV reservoir, the main barrier to HIV eradication. This novel assay, termed TILDA for Tat/rev Induced Limiting Dilution Assay, requires only 10 ml of blood, does not necessitate extraction of viral nucleic acids, is highly reproducible, covers a wide dynamic range of reservoir sizes and can be completed in two days. As such, TILDA may represent an alternative to existing assays used to evaluate the efficacy of therapeutic strategies aimed at reducing the size of the latent HIV reservoir.


Neuronal injuries evidenced by transient cortical magnetic resonance enhancement in hemiplegic migraine: A case report.
Magnetic resonance imaging abnormalities in hemiplegic migraine have been described previously but were limited to a cortical thickening and biphasic alternation of hypoperfusion and hyperperfusion. Our report reveals possible blood-brain barrier disruption during migraine. We present the first demonstrated case of regressive diffuse hemispheric cortical enhancement in sporadic hemiplegic migraine, with histological correlation revealing neuronal lesions similar to ischemic lesions. This is probably due to the severity of the attack as indicated by the left hemiplegia and transient altered consciousness in our 43-year-old male patient. Cortical contrast enhancement on 3D T1 images may suggest migraine severity and be predictive of neuronal loss.


[Algorithms and urinary incontinence in the elderly. Assessment, treatment, recommendations and levels of evidence. Review].
Search processing algorithms in a primary care setting, analyzing the specifics of care management for seniors suffering from urinary incontinence (UI), described the recommendations and levels of evidence of treatment. A literature review carried out via PubMed® and websites of scientific societies with search keywords classified according to an algorithm. One hundred algorithms have been discovered in the field of evaluation and treatment of UI. Screening for UI risk factors began early on in the treatment of reversible or chronic comorbidities, avoiding iatrogenic. Specific clinical features (red flags) required specialized advice. Non-pharmacological conservative treatment should be offered first in line for seniors: behavioral therapy, changes in lifestyle, walk, treatment of constipation. For women, pelvic floor muscle training combined biofeedback and functional electrical stimulation. After failure and persistence of UI with urgency, the information of the risk of a possible urinary retention or cognitive impairments preceded the prescription of an anticholinergic and the measurement of post-voiding residue done by ultrasounds. Older age is not a cons-indication for surgery UI least invasive. The cough test and Bonney maneuver can confirm a masked stress urinary incontinence and/or an associated prolapse. Cases of failure of UI, doubtful diagnosis or programmed surgery required urodynamic assessment. Algorithms and recommendations of UI should remain a valuable aid to the clinical assessment, diagnosis and treatment of UI in the elderly.


Adipose-tissue-derived Stem Cells Enhance the Healing of Ischemic Colonic Anastomoses: An Experimental Study in Rats.
This experimental study verified the effect of adipose-tissue-derived stem cells (ASCs) on the healing of ischemic colonic anastomoses in rats. ASCs were isolated from the subcutaneous fat tissue of rats and identified as mesenchymal stem cells by identification of different potentials. An animal model of colonic ischemic anastomosis was induced by modifying Nagahata's method. Sixty male Sprague-Dawley rats (10-week-old, 370 ± 50 g) were divided into two groups (n = 30 each): a control group in which the anastomosis was sutured in a single layer with 6-0 polypropylene without any treatment and an ASCtreated group (ASC group) in which the anastomosis was sutured as in the control group, but then ASCs were locally transplanted into the bowel wall around the anastomosis. The rats were sacrificed on postoperative day 7. Healing of the anastomoses was assessed by measuring loss of body weight, wound infection, anastomotic leakage, mortality, adhesion formation, ileus, anastomotic stricture, anastomotic bursting pressure, histopathological features, and microvascular density. No differences in wound infection, anastomotic leakage, or mortality between the two groups were observed. The ASC group had significantly more favorable anastomotic healing, including less body weight lost, less ileus, and fewer ulcers and strictures, than the control group. ASCs augmented bursting pressure and collagen deposition. The histopathological features were significantly more favorable in the ASC group, and microvascular density was significantly higher than it was in the control group. Locally-transplanted ASCs enhanced healing of ischemic colonic anastomoses by increasing angiogenesis. ASCs could be a novel strategy for accelerating healing of colonic ischemic risk anastomoses.


Age-related Bruch's membrane change: a clinical study of the relative role of heredity and environment.
For many years there has been controversy concerning the role of genetic influences in the pathogenesis of age-related macular disease. It is widely believed that the lesions causing visual loss occur in response to age-related changes in Bruch's membrane which are recognised clinically as drusen. In this study the density, size, and confluence of drusen as shown on colour photographs were compared in eyes of 50 spouses and 53 sibling pairs ascertained during a prospective study of age-related macular disease. Concordance between pairs of drusen--number, size, and density-were determined by kappa statistic and chi 2 test for trend. Drusen were absent in one sibling and 26 spouses of patients. There was a trend towards concordance of drusen characteristics between siblings but not between spouses, although the difference achieved 5% significance only for the number and density of drusen in the central macula. The difference of concordance between the probands and spouses and the probands and siblings was significant for all characteristics. These findings support the belief that genetic factors influence age-related changes in Bruch's membrane. They also imply that environmental factors are less important or alternatively that the environmental variation between households included in our study was not great enough to be evident.


The design of the neutron radiography and tomography facility at the new research reactor FRM-II at Technical University Munich.
The new reactor FRM-II of Technical University Munich will offer a professional radiography and tomography facility for industrial use. The concept of the instrument and the optimization under the conditions imposed by the surrounding instruments are described for the first installment and for a second stage in an external experimental hall in about 5 years. Several detector systems for different applications will be employed and a short description of their possibilities is given.


A new organic solvent for use in the clearing of tissues. I. Soft tissue histology.
Histosol is a non-flammable solvent mixture of synthetic aromatic hydrocarbons with a flash point of 124 degrees F (T.C.C.). It has a lower vapor pressure and evaporation rate than other organic solvents, such as xylene, routinely used as clearing and deparaffinizing agents. Although both xylene and Histosol clear and deparaffinize soft organ tissues effectively in the preparation of permanently mounted stained slides, Histosol appears, in many instances, to be the choice solvent: tissues are easier to section; cell borders and cell surface modifications are most distinct; cytoplasmic eosinophilia is more vivid; and nuclear detail is improved. Of prime importance, Histosol is a safer and more efficient solvent for use in histological and pathological laboratories.


Mentha piperita (Linn.) leaf extract provides protection against radiation induced chromosomal damage in bone marrow of mice.
Oral administration of M. piperita (1 g/kg body weight/day) before exposure to gamma radiation was found to be effective in protecting against the chromosomal damage in bone marrow of Swiss albino mice. Animals exposed to 8 Gy gamma radiation showed chromosomal aberrations in the form of chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges and acentric fragments. There was a significant increase in the frequency of aberrant cells at 6 hr after irradiation. Maximum aberrant cells were observed at 12 hr post-irradiation autopsy time. Further, the frequency of aberrant cells showed decline at late post-irradiation autopsy time. However, in the animals pretreated with Mentha extract, there was a significant decrease in the frequency of aberrant cells as compared to the irradiated control. Also significant increase in percentage of chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges, acentric fragments, total aberrations and aberrations/damaged cell was observed at 12 hr post-irradiation autopsy time in control animals, whereas Mentha pretreated irradiated animals showed a significant decrease in percentage of such aberrations. A significant decrease in GSH content and increase in LPO level was observed in control animals, whereas Mentha pretreated irradiated animals exhibited a significant increase in GSH content and decrease in LPO level but the values remained below the normal. The radioprotective effect of Mentha was also demonstrated by determining the LD(50/30) values (DRF = 1.78). The results from the present study suggest that Mentha pretreatment provides protection against radiation induced chromosomal damage in bone marrow of Swiss albino mice.


Atypical rabies with MRI findings: clue to the diagnosis.
Rabies is known for most as a fatal infectious disease, mainly transmitted to both humans and animals through bites by rabid animals. In its classical form, rabies is well recognised, but when it presents atypically in paralytic form, it may become difficult to distinguish from Guillain-Barré syndrome (GBS) or myelitis, particularly where history is not forthcoming or concealed. The authors report here an atypical case of paralytic rabies presenting with descending paralysis followed by furious form where clue to suspicion was MRI findings. Imaging in rabies is seldom done. MRI findings of rabies encephalitis are well known, but in myelitis these need to be further characterised. The authors present MRI findings in a confirmed case of rabies myelitis. The differential diagnosis of the imaging findings as well as the role and the relevance of imaging in the diagnosis of this disease are discussed.


Atorvastatin and clopidogrel interfere with photosensitization in vitro.
Photodynamic therapy (PDT) has been used to eliminate undesired cells by using a combination of photosensitizers and light illumination to generate reactive oxygen species. There is great interest in applying PDT to atherosclerosis; preferential destruction of pro-inflammatory macrophages in atheromata might attenuate plaque growth or rupture-prone vulnerability. Here, we report on a previously unknown interaction between cardiovascular drugs that are commonly prescribed for atherosclerosis patients and the cytolytic effects of photodynamic therapy using Cathepsin B activatable photosensitizer L-SR15 on murine macrophage Raw 264.7 cells in culture. Atorvastatin and clopidogrel significantly interfered with in vitro photosensitization effect while aspirin did this to a lesser extent; these drugs did not change the efficiency of cellular uptake of L-SR15 after in vitro photosensitization. A photosensitization interference effect of atorvastatin and clopidogrel was also observed when using a conventional photosensitizer free Ce6 or NCI-H1299 cancer cells. Considering the clinical implications of PDT, our study merits further investigation in clinical settings as well as in animal models.


Circulating blood volume determination using electronic spin resonance spectroscopy.
There have been numerous methods proposed to measure the circulating blood volume (CBV). Nevertheless, none of them have been massively and routinely accepted in clinical diagnosis. This study describes a simple and rapid method, on a rabbit model, using the dilution of autologous red cells labeled with a nitroxide radical (Iodoacetamide-TEMPO), which can be detected by electronic spin resonance (ESR) spectroscopy. Blood samples were withdrawn and re-injected using the ears' marginal veins. The average CBV measured by the new method/body weight (CBV(IAT)/BW) was 59 +/- 7 mL/kg (n = 33). Simultaneously, blood volume determinations using the nitroxide radical and (51)Cr (CBV(Cr)) were performed. In the plot of the difference between the methods (CBV(IAT) - CBV(Cr)) against the average (CBV(IAT) + CBV(Cr))/2, the mean of the bias was -1.1 +/- 6.9 mL and the limits of agreement (mean difference +/-2 SD) were -14.9 and 12.7 mL. Lin's concordance correlation coefficient p(c) = 0.988. Thus, both methods are in close agreement. The development of a new method that allows a correct estimation of the CBV without using radioactivity, avoiding blood manipulation, and decreasing the possibility of blood contamination with similar accuracy and precision of that of the "gold standard method" is an innovative proposal.


Determining Minimum Inhibitory Concentrations in Liquid Cultures or on Solid Medium.
Antimicrobial susceptibility testing is the mainstay of tuberculosis drug development programs. In this chapter, we describe methods for determination of the minimum inhibitory concentration of compounds against Mycobacterium tuberculosis growing in liquid media as a function of carbon source, detergent, and environmental stress imposed by acidic pH as well as reactive nitrogen intermediates. Methods for determining the effect of bovine serum albumin in the growth medium on antimicrobial susceptibility are also described. Finally, we provide a method for antimicrobial susceptibility testing on agar medium.


Surgical treatment of retinal detachment associated with degenerative retinoschisis.
Although degenerative retinoschisis is almost always asymptomatic, retinal detachment occurs in some patients with outer layer breaks (OLBs). The purpose of this study is to evaluate the different surgical techniques used for the treatment of this condition. Retrospective interventional case series. The patients underwent either a Scleral-Buckling procedure (SB) or a 3-port pars plana vitrectomy (V). Pre-, intra-, and post-operative data were analyzed for the two groups. Thirty eyes of 30 consecutive patients were included in the analysis. There was a statistically significant difference (0.5 ± 0.48 LogMAR units for the SB group, 1.37 ± 1.4 LogMAR units for the V group, p = 0.027) in final BCVA when the two groups were compared, whereas there was no statistically significant difference in the baseline BCVA between the two groups (p = 0.38). The proportion of cases that were successfully attached with one operation was slightly lower in the V group (62% versus 76%). Conversely, the proportion of cases that were successfully attached with more than one operation was similar in both groups (23% and 24%, respectively). The present study highlights that retinoschisis-associated RD is a demanding situation to treat and remains a challenge for vitreoretinal surgeons. Scleral buckle procedure was found to be successful in eyes that have peripheral OLBs and not extensive RDs, and PPV should be considered for treating symptomatic, rather extensive schisis-RDs, especially in cases with large or posterior outer layer breaks.


A chronic rejection model and potential biomarkers for vascularized composite allotransplantation.
Chronic rejection remains the Achilles heel in vascularized composite allotransplantation. Animal models to specifically study chronic rejection in vascularized composite allotransplantation do not exist so far. However, there are established rat models to study chronic rejection in solid organ transplantation such as allogeneic transplantation between the rat strains Lewis and Fischer344. Thus, we initiated this study to investigate the applicability of hindlimb transplantation between these strains to imitate chronic rejection in vascularized composite allotransplantation and identify potential markers. Allogeneic hindlimb transplantation were performed between Lewis (recipient) and Fischer344 (donor) rats with either constant immunosuppression or a high dose immunosuppressive bolus only in case of acute skin rejections. Histology, immunohistochemistry, microarray and qPCR analysis were used to detect changes in skin and muscle at postoperative day 100. We were able to demonstrate significant intimal proliferation, infiltration of CD68 and CD4 positive cells, up-regulation of inflammatory cytokines and initiation of muscular fibrosis in the chronic rejection group. Microarray analysis and subsequent qPCR identified CXC ligands 9-11 as potential markers of chronic rejection. The Fischer344 to Lewis hindlimb transplantation model may represent a new option to study chronic rejection in vascularized composite allotransplantation in an experimental setting. CXC ligands 9-11 deserve further research to investigate their role as chronic rejection markers.


Measurement of peripapillary retinal nerve fiber layer thickness and macular thickness in anisometropia using spectral domain optical coherence tomography: a prospective study.
To study whether there is a difference in central macular thickness (CMT) and peripapillary retinal nerve fiber layer (RNFL) thickness between the two eyes of individuals having anisometropia >1 diopter (D) using spectral domain optical coherence tomography (OCT). One hundred and one subjects, 31 with myopic anisometropia, 28 with astigmatic anisometropia, and 42 with hypermetropic anisometropia, were enrolled in the study. After informed consent, detailed ophthalmological examination was performed for every patient including cycloplegic refraction, best corrected visual acuity, slit lamp, and fundus examination. After routine ophthalmic examination peripapillary RNFL and CMT were measured using spectral domain OCT and the values of the two eyes were compared in the three types of anisometropia. Axial length was measured using an A Scan ultrasound biometer (Appa Scan-2000). The average age of subjects was 21.7±9.3 years. The mean anisometropia was 3.11±1.7 D in myopia; 2±0.99 D in astigmatism; and 3.68±1.85 D in hypermetropia. There was a statistically significant difference in axial length of the worse and better eye in both myopic and hypermetropic anisometropia (P=0.00). There was no significant difference between CMT of better and worse eyes in anisomyopia (P=0.79), anisohypermetropia (P=0.09), or anisoastigmatism (P=0.16). In anisohypermetropia only inferior quadrant RNFL was found to be significantly thicker (P=0.011) in eyes with greater refractive error. There does not appear to be a significant difference in CMT and peripapillary RNFL thickness in anisomyopia and anisoastigmatism. However, in anisohypermetropia inferior quadrant RNFL was found to be significantly thicker.


Expression of cholesterol packaging and transport genes in human and rat placenta: impact of obesity and a high-fat diet.
Evidence suggests that sub-optimal maternal nutrition has implications for the developing offspring. We have previously shown that exposure to a low-protein diet during gestation was associated with upregulation of genes associated with cholesterol transport and packaging within the placenta. This study aimed to elucidate the effect of altering maternal dietary linoleic acid (LA; omega-6) to alpha-linolenic acid (ALA; omega-6) ratios as well as total fat content on placental expression of genes associated with cholesterol transport. The potential for maternal body mass index (BMI) to be associated with expression of these genes in human placental samples was also evaluated. Placentas were collected from 24 Wistar rats at 20-day gestation (term = 21-22-day gestation) that had been fed one of four diets containing varying fatty acid compositions during pregnancy, and from 62 women at the time of delivery. Expression of 14 placental genes associated with cholesterol packaging and transfer was assessed in rodent and human samples by quantitative real time polymerase chain reaction. In rats, placental mRNA expression of ApoA2, ApoC2, Cubn, Fgg, Mttp and Ttr was significantly elevated (3-30 fold) in animals fed a high LA (36% fat) diet, suggesting increased cholesterol transport across the placenta in this group. In women, maternal BMI was associated with fewer inconsistent alterations in gene expression. In summary, sub-optimal maternal nutrition is associated with alterations in the expression of genes associated with cholesterol transport in a rat model. This may contribute to altered fetal development and potentially programme disease risk in later life. Further investigation of human placenta in response to specific dietary interventions is required.


The importance of social intervention in England's mortality decline: the evidence reviewed.
This paper examines the first phase of England's mortality decline, which commenced in the middle of the eighteenth century, and proceeded fitfully down to the end of the nineteenth. It finds that recent research in population history has weakened the explanation known as the McKeown thesis, but that the alternative synthesis, developed by Szreter, does not stand up well to a scrutiny of the evidence on infant mortality and morbidity. It concludes by pointing out that, contrary to the received version, diarrhoeal diseases continued in defiance of late-Victorian public health measures, but appear to have become less lethal, sharing in the general decline in the lethality of illness found by J. C. Riley for the second half of the nineteenth century.


Tunneling Effect That Changes the Reaction Pathway from Epoxidation to Hydroxylation in the Oxidation of Cyclohexene by a Compound I Model of Cytochrome P450.
The rate constants of the C═C epoxidation and the C-H hydroxylation (i.e., allylic C-H bond activation) in the oxidation of cyclohexene by a high-valent iron(IV)-oxo porphyrin π-cation radical complex, [(TMP•+)FeIV(O)(Cl)] (1, TMP = meso-tetramesitylporphyrin dianion), were determined at various temperatures by analyzing the overall rate constants and the products obtained in the cyclohexene oxidation by 1, leading us to conclude that reaction pathway changes from the C═C epoxidation to C-H hydroxylation by decreasing reaction temperature. When cyclohexene was replaced by deuterated cyclohexene (cyclohexene-d10), the epoxidation pathway dominated irrespective of the reaction temperature. The temperature dependence of the rate constant of the C-H hydroxylation pathway in the reactions of cyclohexene and cyclohexene-d10 by 1 suggests that there is a significant tunneling effect on the hydrogen atom abstraction of allylic C-H bonds of cyclohexene by 1, leading us to propose that the tunneling effect is a determining factor for the switchover of the reaction pathway from the C═C epoxidation pathway to the C-H hydroxylation pathway by decreasing reaction temperature. By performing density functional theory (DFT) calculations, the reaction energy barriers of the C═C epoxidation and C-H bond activation reactions by 1 were found to be similar, supporting the notion that small environmental changes, such as the reaction temperature, can flip the preference for one reaction to another.


Effect of Energy Alignment, Electron Mobility, and Film Morphology of Perylene Diimide Based Polymers as Electron Transport Layer on the Performance of Perovskite Solar Cells.
For organic-inorganic perovskite solar cells (PerSCs), the electron transport layer (ETL) plays a crucial role in efficient electron extraction and transport for high performance PerSCs. Fullerene and its derivatives are commonly used as ETL for p-i-n structured PerSCs. However, these spherical small molecules are easy to aggregate with high annealing temperature and thus induce morphology stability problems. N-type conjugated polymers are promising candidates to overcome these problems due to the tunable energy levels, controllable aggregation behaviors, and good film formation abilities. Herein, a series of perylene diimide (PDI) based polymers (PX-PDIs), which contain different copolymeried units (X), including vinylene (V), thiophene (T), selenophene (Se), dibenzosilole (DBS), and cyclopentadithiophene (CPDT), are introduced as ETL for p-i-n structured PerSCs. The effect of energy alignment, electron mobility, and film morphology of these ETLs on the photovoltaic performance of the PerSCs are fully investigated. Among the PX-PDIs, PV-PDI demonstrates the deeper LUMO energy level, the highly delocalized LUMO electron density, and a better planar structure, making it the best electron transport material for PerSCs. The planar heterojunction PerSC with PV-PDI as ETL achieves a power conversion efficiency (PCE) of 10.14%, among the best values for non-fullerene based PerSCs.


Termination of Ca²+ release for clustered IP₃R channels.
In many cell types, release of calcium ions is controlled by inositol 1,4,5-trisphosphate (IP₃) receptor channels. Elevations in Ca²⁺ concentration after intracellular release through IP₃ receptors (IP₃R) can either propagate in the form of waves spreading through the entire cell or produce spatially localized puffs. The appearance of waves and puffs is thought to implicate random initial openings of one or a few channels and subsequent activation of neighboring channels because of an "autocatalytic" feedback. It is much less clear, however, what determines the further time course of release, particularly since the lifetime is very different for waves (several seconds) and puffs (around 100 ms). Here we study the lifetime of Ca²⁺ signals and their dependence on residual Ca²⁺ microdomains. Our general idea is that Ca²⁺ microdomains are dynamical and mediate the effect of other physiological processes. Specifically, we focus on the mechanism by which Ca²⁺ binding proteins (buffers) alter the lifetime of Ca²⁺ signals. We use stochastic simulations of channel gating coupled to a coarse-grained description for the Ca²⁺ concentration. To describe the Ca²⁺ concentration in a phenomenological way, we here introduce a differential equation, which reflects the buffer characteristics by a few effective parameters. This non-stationary model for microdomains gives deep insight into the dynamical differences between puffs and waves. It provides a novel explanation for the different lifetimes of puffs and waves and suggests that puffs are terminated by Ca²⁺ inhibition while IP₃ unbinding is responsible for termination of waves. Thus our analysis hints at an additional role of IP3 and shows how cells can make use of the full complexity in IP₃R gating behavior to achieve different signals.


Bet v 1-displaying elastin-like polypeptide nanoparticles induce a strong humoral and weak CD4+ T-cell response against Bet v 1 in a murine immunogenicity model.
There is growing concern about the toxicity of colloidal aluminum salts used as adjuvants in subcutaneous allergen immunotherapy (SCIT). Therefore, alternative adjuvants and delivery systems are being explored to replace alum in SCIT. We applied micellar elastin-like polypeptides (ELPs), a type of self-assembling protein, to replace alum as vaccine adjuvant in birch pollen SCIT. ELP and an ELP-Bet v 1 fusion protein were expressed in E. coli and purified by immuno-affinity chromatography and inverse-transition cycling (ITC). Nanoparticles self-assembled from ELP and a 9:1 ELP/ELP-Bet v 1 mixture were characterized by using dynamic light scattering and atomic force microscopy. Allergenicity was assessed by measuring mediator release from rat basophilic leukemia cells transformed with the human FcϵR1 and sensitized with sera derived from human birch pollen allergic patients. Humoral and T-cell immunity were investigated by immunizing naïve mice with the ELP/ELP-Bet v 1 nanoparticles or alum-adsorbed Bet v 1, both containing 36 µg Bet v 1. ELP and ELP/ELP-Bet v 1 self-assembled at 37°C into spherically shaped micelles with a diameter of ~45 nm. ELP conjugation made Bet v 1 hypo-allergenic (10-fold). Compared to alum-adsorbed Bet v 1, ELP/ELP-Bet v 1 nanoparticles induced stronger IgG responses with an earlier onset. Additionally, ELP/ELP-Bet v 1 did not induce Th2 skewing cytokines and IgE. The hypoallergenic character and strong humoral immune response in the absence of a Th2-skewing T-cell response make ELP-based nanoparticles a promising candidate to replace alum in SCIT.


Meningiomas: Overview and New Directions in Therapy.
The majority of meningiomas, the most common primary brain tumor, are considered to be benign, and characteristic magnetic resonance imaging features allow a preliminary diagnosis. Meningiomas can be classified in the World Health Organization system as grade I, II, or III, depending on various histological features. In many cases, observation is the preferred management option, although this means the absence of a histological diagnosis. If necessary, standard therapy consists of surgery with or without adjuvant radiation, depending on the tumor grade and the degree of resection. To date, systemic therapies are not included in the standard of care. The level of evidence for treatment recommendations is low, and effective treatment regimens, especially for surgery-refractory and radiation-refractory meningiomas, are still very limited. Recent studies have broadened our knowledge of the genetics and pathogenesis of meningiomas and will lead to new therapeutic options. This review summarizes the epidemiology, pathogenesis and genetics, classification, and diagnosis of meningiomas, as well as management principles, including promising new avenues of therapy.


The complete nucleotide sequence of Malabar grouper (Epinephelus malabaricus) mitochondrial genome.
In this study, we reported the complete mitochondrial DNA sequence of the Epinephelus malabaricus. The full-length of the mitochondrial genome consisted of a 16,423 bp fragment, with the base composition of A (28.70%), T (26.55%), G (15.92%) and C (28.83%). It contained 2 rRNA genes, 13 protein-coding genes, 22 tRNA genes and a major non-coding control region (D-loop region). The composition and order of these genes were identical to most of other vertebrates. All the protein initiation codons were ATG, except that COX1 began with GTG, ATP-6 and ND6 was not determined, respectively. The complete mitogenome of the Epinephelus malabaricus provided an important data set for the study in genetic mechanism of the hybridization.


Reproducibility of the EGFR immunohistochemistry scores for tumor samples from patients with advanced non-small cell lung cancer.
Epidermal growth factor receptor (EGFR) is overexpressed in >60% of non-small cell lung cancer (NSCLC) cases. In combination with radiotherapy or chemotherapy, first-line treatments with antibodies against EGFR, including cetuximab and necitumumab, have demonstrated benefits by increasing overall survival (OS), particularly in patients who overexpress EGFR. The present study evaluated the interobserver agreement among three senior pathologists, who were blinded to the clinical outcomes and assessed tumor samples from 85 patients with NSCLC using the H-score method. EGFR immunohistochemistry was performed using a qualitative immunohistochemical kit. The reported (mean ± standard deviation) H-scores from each pathologist were 111±102, 127±103 and 128.53±104.03. The patients with average H-scores ≥1, ≥100, ≥200 and between 250-300 were 85.9, 54.1, 28.2 and 12.9, respectively. Patients who had an average H-score >100 had a shorter OS time compared with those with lower scores. Furthermore, patients with EGFR mutations who were treated with EGFR-tyrosine kinase inhibitors (TKIs) and had an average H-score >100 had a longer OS time compared with those with an average H-score <100. The interobserver concordance for the total H-scores were 0.982, 0.980 and 0.988, and for a positive H-score ≥200, the interobserver concordance was 0.773, 0.710 and 0.675, respectively. The determination of EGFR expression by the H-score method is highly reproducible among pathologists and is a prognostic factor associated with a poor OS in all patients. Additionally, the results of the present study suggest that patients with EGFR mutations that are treated with EGFR-TKIs and present with a high H-score have a longer OS time.


The novel strategy for concurrent chemoradiotherapy by conjugating the apoptotic cell-binding moiety to caspase-3 activated doxorubicin prodrug.
The selective targeting of cytotoxic agents to a tumor has shown limited success by difficulties in identifying the appropriate target molecules, and more importantly, by the phenotypically dynamic nature of the tumor cells and intratumoral heterogeneity. In an attempt to overcome these issues and efficiently deliver cytotoxic drugs to the tumor, we previously reported a strategy termed radiation-induced apoptosis-targeted chemotherapy (RIATC), which utilizes the radiotherapy for intentionally triggering the caspase-3 and in situ amplification of tumor apoptosis by caspase-3 activated prodrug. Herein, we propose an advanced form of RIATC prodrug, AP1-DEVD-S-DOX, that could more actively target to the ligands of radiation-induced tumor cells, which could accumulate more prodrugs, thereby allowing more effective in situ activation and amplification of tumor apoptosis, comparing to RIATC. Indeed, AP1-DEVD-S-DOX was able to exert improved doxorubicin (DOX) delivery to the tumor and anticancer effect than the RIATC prodrug that lacks apoptotic cell-binding property but having a similar degree of off-target distribution in the other organs. Accordingly, AP1-DEVD-S-DOX could be an efficient prodrug for concurrent chemoradiotherapy by selectively delivering doxorubicin to the tumor with less systemic cytotoxicity.


Raloxifene increases the capacity of serum to promote prostacyclin release in human endothelial cells: implication of COX-1 and COX-2.
Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase in endothelium. The aim of this study was to investigate the effect of serum from postmenopausal women treated with raloxifene on prostacyclin production by human umbilical vein endothelial cells and on cyclooxygenases-1 and -2. Serum was collected from 21 women receiving 60 mg/day of raloxifene, at baseline and at 3 and 6 months. Human umbilical vein endothelial cells were exposed to serum for 24 hours, and prostacyclin production was evaluated in supernatants. Selective inhibitors of cyclooxygenases-1 and -2 (SC-560 and NS-398) were used to investigate the relative contribution of each enzyme. Protein expression for each enzyme was determined using Western blot assays. Prostacyclin production was increased by 30% (P < or = 0.001) when serum from women treated for 3 and 6 months was added. SC-560 reversed prostacyclin production but did not change baseline values. NS-398, in turn, reduced prostacyclin production using sera from baseline, 3 and 6 months. Cyclooxygenases-1 and -2 protein expression remained unaltered at each treatment step. Serum from women treated with raloxifene stimulated prostacyclin release from human umbilical vein endothelial cells in culture, an effect that seems mediated by increased cyclooxygenase-1 activity.


Clinical Usefulness of Tools to Support Decision-making for Palliative Treatment of Metastatic Colorectal Cancer: A Systematic Review.
Decision-making regarding palliative treatment for patients with metastatic colorectal cancer (mCRC) is complex and comprises numerous decisions. Decision-making should be guided by the premise of maintaining and/or improving patients' quality of life, by patient preference, and by the trade-off between treatment benefits and harm. Decision support systems (DSSs) for clinicians (eg, nomograms) can assist in this process. The present systematic review aimed to provide a comprehensive overview of the available DSSs for incurable mCRC and to assess their clinical usefulness. A systematic literature search was performed in PubMed, Embase, and the Cochrane Library. We extracted information on the DSS characteristics and their discriminatory ability, calibration, and user-friendliness. From 5205 studies, we identified 14 DSSs for decisions regarding palliative resection of the primary tumor (n = 3), radiotherapy for metastases (n = 2), treatment type (invasive vs. symptomatic only; n = 7), and selection of chemotherapy (n = 2). The predictors varied greatly among the DSSs, and only 1 DSS incorporated a genetic marker (ie, UGT1A1). None of the DSSs included > 1 treatment option, nor did any DSS present estimates of treatment benefits and harms. Five tools had not been externally validated, two had only been validated in < 35 patients, and the rest had only been validated in populations similar to the population used for their development. Discriminatory accuracy was generally moderate to poor. Calibration measures were only reported for 2 tools. A limited number of DSSs are available to support palliative treatment decisions for patients with mCRC, and the evidence regarding their discriminatory ability and calibration is too limited to recommend their use. New DSSs comparing multiple treatment options and presenting both treatment benefits and harms are needed.


Influence of molecular classification in anaplastic glioma for determining outcome and future approach to management.
Assess survival of patients with anaplastic glioma (AG) and the relationship to molecular subtype. Patients with AG managed with IMRT between 2008 and 2014 were entered into a prospective database assessing relapse-free survival (RFS) and overall survival (OS). Isocitrate dehydrogenase (IDH) mutations were assessed prospectively from 2011, and subsequent testing of historical patients allowing categorisation under WHO 2016 classification as anaplastic astrocytoma IDH wild type (AAwt), anaplastic astrocytoma IDH mutated (AAmut), anaplastic oligodendroglioma (AOD) or other glial tumour (OTH). Kaplan-Meier estimates of survival distribution were calculated for the primary endpoint of overall survival and Log-rank test used to determine associated factors. One hundred and fifty-six patients were included with median follow-up for survivors of 4.7 years. Fifty-six per cent were managed after initial diagnosis, whilst 18% received IMRT at second or later relapse. Seventy-three per cent had temozolomide as part of initial therapy. A total of 118 or 75% of patients had IDH mutated glioma, of which 61 were AOD and 57 AAmut. There were 68 relapses and 52 deaths for a 6yrRFS of 51.2% and 6yrOS of 62.5%. AAwt was associated with worse survival (P < 0.001); and delay of RT until second or later relapse (P = 0.03). Within the 118 patients with IDH mutated tumours, 6yrOS for AOD and AAmut were 90.0% and 62.5%, respectively (P = 0.003). Also two or more craniotomies (P < 0.001), delayed RT (P = 0.006) and age <40 years (P = 0.022) were associated with worse survival on univariate analysis but only AAmut subtype and number of craniotomies on multivariate analysis. Within AG, molecular classification predicts for survival, and should influence current decision-making.


Gender differences in landing mechanics vary depending on the type of landing.
Men and women exhibit different movement patterns, which are thought to contribute to the increased incidence of anterior cruciate ligament injuries in females. Although gender differences have been observed in movement, few studies have examined gender differences during different types of landings. Prospective gender comparison study. Controlled laboratory study. Fourteen male and 14 female recreational soccer players were recruited for the study. All subjects performed a soccer-specific jump heading activity to examine differences in landing mechanics before and after heading the soccer ball. Subjects began the task by performing a forward jump onto 2 force platforms (landing 1) and conducting a countermovement before jumping up to head a soccer ball that was hanging above the force platform before, then landing back on the force platforms (landing 2). A 2-way analysis of variance (gender × landing) was performed to examine the interaction between gender and different types of landings on sagittal plane joint mechanics. Significant interactions existed for the peak hip extension moment and vertical ground reaction force where the male players exhibited increased values during the second landing compared with the female players. Males exhibited greater peak plantarflexion and knee extension moments, but decreased peak hip flexion. Main effects for landing exhibited lower kinematic and larger kinetic values except for the peak plantarflexion moment. Female and male players appear to land differently depending on the type of landing. Therefore, specificity of landing type may be important to consider when screening for injury risk factors. This study examines the differences between genders during 2 different landing tasks and demonstrates the importance of considering the jumping task when screening individuals for injury risk factors.


High temperatures change the perspective: Integrating hormonal responses in citrus plants under co-occurring abiotic stress conditions.
Plants growing in the field are subjected to multiple stress factors acting simultaneously. Abnormally high temperatures are expected to affect wild plants and crops in the next years due to global warming. In this work, we have studied physiological, hormonal and molecular responses of the citrus rootstock, Carrizo citrange (Poncirus trifoliata L. Raf. × Citrus sinensis L. Osb.) subjected to wounding or high salinity occurring individually or in combination with heat stress. According to our results, combination of high salinity and heat stress aggravated the negative effects of salt intoxication in Carrizo. The high transpiration rate caused by high temperatures counteracted physiological responses of plants to salt stress and increased Cl- intake in leaves. In addition, 12-oxo-phytodienoic acid accumulated specifically under combination of wounding and heat stress, whereas at low temperatures, wounded plants accumulated jasmonic acid (JA) and JA-isoleucine (JA-Ile). Moreover, an antagonism between salicylic acid (SA) and JA was observed, and wounded plants subjected to high temperatures did not accumulate JA nor JA-Ile whereas SA levels increased (via isochorismate synthase biosynthetic pathway). Wounded plants did not accumulate abscisic acid (ABA) but its catabolite phaseic acid. This could act as a signal for the upregulation of (ABA)-RESPONSIVE ELEMENT (ABRE)-BINDING TRANSCRIPTION FACTOR 2 (CsAREB2) and RESPONSIVE TO DISSECATION 22 (CsRD22) in an ABA-independent way. This work uncovers some mechanisms that explain Carrizo citrange tolerance to high temperatures together with different hormonal signals in response to specific stresses. It is suggested that co-occurring abiotic stress conditions can modify (either enhance or reduce) the hormonal response to modulate specific responses.


A non-static quantum inspired spacetime in f(R) gravity: Gravity's rainbow.
In this note we explore a non-static spacetime in quantum regime in the background of f ( R ) gravity. The time dependent Vaidya metric which represents the spacetime of a radiating body like star is studied in an energy dependent gravity's rainbow, which is a UV completion of General Relativity. In our quest we have used gravitational collapse as the main tool. The focus is to probe the nature of singularity (black hole or naked singularity) formed out of the collapsing procedure. This is achieved via a geodesic study. For our investigation we have considered two different models of f ( R ) gravity, namely the inflationary Starobinsky's model and the power law model. Our study reveals the fact that naked singularity is as good a possibility as black hole as far as the central singularity is concerned. Via a proper fine tuning of the initial data, we may realize both black hole or naked singularity as the end state of the collapse. Thus this study is extremely important and relevant in the light of the Cosmic Censorship hypothesis. The most important result derived from the study is that gravity's rainbow increases the tendency of formation of naked singularities. We have also deduced the conditions under which the singularity will be a strong or weak curvature singularity. Finally in our quest to know more about the model we have performed a thermodynamical study. Throughout the study we have obtained results which involve deviation from the classical set-up. Such deviations are expected in a quantum evolution and can be attributed to the quantum fluctuations that our model suffers from. It is expected that this study will enhance our knowledge about quantization of gravity and subsequently about the illusive theory of quantum gravity.


[Determination of total sulfur in coal by ion chromatography].
To develop a method for determination of total sulfur in coal by ion chromatography. To pretreat the coal by high-temperature combustion with oxygen-flow in tube furnace, and the sulfur with any from in coal was oxidated and converted into oxid of sulfur, which became sulfate after oxidated by H2O2 absorption solution. The separation of sulfate was achieved on DionexAS12A anion exchange column with a carbonate eluent, and the detection is performed by the suppressed conductivity detector with the injection volume of 50 microl. The total sulfur in coals were obtained from the determined results. The method had been compared with the National Standard Method "High-Temperature Combustion--Neutralization Method for Determination of Total Sulfur in Coal (GB/T214-1996)", and the RSD of the method was less than 2% . This method had good relativity of the linearity (r = 0.9998) at the range of 0 to approximately 15 microg/ml for sulfate. Two kinds of national certified reference materials (GBW11104c and GBWl1110d) were determined, and the RSD were 1.92% and 0.47% respectively. Ion chromatography for determination of total sulfur in coal has simple operation, high accuracy, and fast analysis, and can be applied in determination of total sulfur in coal.


Evolution of a symbiotic receptor through gene duplications in the legume-rhizobium mutualism.
The symbiosis between legumes and nitrogen-fixing rhizobia co-opted pre-existing endomycorrhizal features. In particular, both symbionts release lipo-chitooligosaccharides (LCOs) that are recognized by LysM-type receptor kinases. We investigated the evolutionary history of rhizobial LCO receptor genes MtLYK3-LjNFR1 to gain insight into the evolutionary origin of the rhizobial symbiosis. We performed a phylogenetic analysis integrating gene copies from nonlegumes and legumes, including the non-nodulating, phylogenetically basal legume Cercis chinensis. Signatures of differentiation between copies were investigated through patterns of molecular evolution. We show that two rounds of duplication preceded the evolution of the rhizobial symbiosis in legumes. Molecular evolution patterns indicate that the resulting three paralogous gene copies experienced different selective constraints. In particular, one copy maintained the ancestral function, and another specialized into perception of rhizobial LCOs. It has been suggested that legume LCO receptors evolved from a putative ancestral defense-related chitin receptor through the acquisition of two kinase motifs. However, the phylogenetic analysis shows that these domains are actually ancestral, suggesting that this scenario is unlikely. Our study underlines the evolutionary significance of gene duplication and subsequent neofunctionalization in MtLYK3-LjNFR1 genes. We hypothesize that their ancestor was more likely a mycorrhizal LCO receptor, than a defense-related receptor kinase.


MAVRIC based T2 mapping assessment of infrapatellar fat pad scarring in patients with total knee arthroplasty.
The infrapatellar fat pad (IPFP) has been implicated as a source of postoperative knee pain. Imaging the IPFP is challenging in patients with total knee arthroplasty (TKA) due to metallic susceptibility artifact. Multi-Acquisition Variable-Resonance Image Combination (MAVRIC)-based T2 Mapping has been developed to mitigate this artifact and can generate quantitative T2 data. Objectives of this study were to (1) measure T2 values of the IPFP in patients with TKAs using a MAVRIC based T2 mapping technique and (2) determine if IPFP T2 values are related to the degree of fat pad scarring or clinical magnetic resonance imaging (MRI) findings. Twenty-eight subjects (10 males, 18 females, Age: 66 + 7.2 years [Mean ± standard deviations]) undergoing clinical MRIs were sequentially recruited. Morphological imaging and quantitative T2 mapping sequences were performed on a clinical 1.5 T scanner. The morphologic images were graded for the presence and severity of fat pad scarring and clinical outcomes. T2 values were calculated in the total fat pad volume, a normal regions of interest (ROI), and an abnormal ROI. T2 values were shortened in the total IPFP volume (p = 0.001) and within abnormal regions (p = 0.003) in subjects with more severe IPFP scarring. The difference between T2 values in normal-abnormal regions was greater in subjects with severe versus no scarring (+1426.1%, p = 0.008). T2 values were elevated in patients with MRI findings of osteolysis (+32.3%, p = 0.02). These findings indicate that MAVRIC-based T2 Mapping may be used as a quantitative biomarker of postoperative IPFP scarring in individuals following TKA.


Severe hyperuricemia in patients with volume depletion.
Profound hyperuricemia (19-42 (27 +/- 3.3) mg/dl) was noted in seven adult patients with volume depletion and marked prerenal azotemia (SUN, 155 +/- 30 mg/dl and serum creatinine 5.2 +/- 1.1 mg/dl). The serum level of uric acid returned to normal following the administration of 3.2 +/- 0.4 liters of saline/day over a period of 3.4 +/- 0.6 days. Throughout the course of the illness, there were significant correlations (r = 0.83, p less than 0.01) between the serum levels of both urea nitrogen and creatinine and those of uric acid. Because of the rapid reversibility of this hyperuricemia with hydration, it should be differentiated from other clinical conditions associated with acute renal failure and profound hyperuricemia.


Secretin-induced gastrin response in the Zollinger-Ellison syndrome and chronic duodenal ulcer patients before and after cimetidine treatment.
A secretin provocative test was performed in 16 patients with chronic duodenal ulcer and in five patients with the Zollinger-Ellison syndrome. In four chronic duodenal ulcer patients a second secretin test was done during acute iv cimetidine administration. There were only slight variations of gastrin compared with the first test. A third test was done on the same four chronic duodenal ulcer patients after 1 month's po cimetidine treatment (1 g/day); gastrin at 0 time was significantly higher than in the previous two tests (p less than 0.01). Integrated gastrin response after secretin was significantly lower in the third test than in the first (p less than 0.05). In two Zollinger-Ellison syndrome patients treated with 1.0 and 1.4 g/day cimetidine for 3 months, gastrin at 0 time was not markedly increased, whereas compared with the first test gastrin levels were higher at each time after secretin. These data suggest that previous cimetidine treatment does not alter, and may even increase, the diagnostic sensitivity of the secretin test.


Apoptosis affects integration frequency: adult stem cells injected in blastocysts show high caspase-3 activity.
Chimeric organisms are commonly generated by injecting stem cells into blastocysts. Embryonic stem cells injected into the blastocoel cavity participate in the further development of the embryo. Adult stem cells have also been used in injection experiments to study their potential plasticity. In this study we focused on the early fate of injected human adult hematopoietic stem cells (HSCs). HSCs were followed immunohistochemically 1-19 h after injection into murine blastocysts. We found that they only rarely attached and integrated into the blastocysts. The high rate of loss of injected cells after prolonged in vitro culture of the chimeras can be explained by apoptosis. Our findings are consistent with previous studies reporting a low rate of integration of adult cells injected to produce chimeric embryos, but this is the first demonstration that the low efficiency of adult stem cell injections into blastocysts is influenced by apoptosis.


Distinct cytoskeletal modulation and regulation of G1-S transition in the two life stages of Trypanosoma brucei.
Procyclic-form Trypanosoma brucei is arrested in G1 phase with extended and/or branched posterior morphology when expression of its cdc2-related kinases 1 and 2 (CRK1 and CRK2) is knocked down by RNA interference. Transmission electron microscopy indicated that the mitochondrion in the cell is also extended and branched and associated with cortical microtubules in each elongated/branched posterior end. This posterior extension is apparently driven by the growing microtubule corset, as it can be blocked by rhizoxin, an inhibitor of microtubule assembly. In the bloodstream form of T. brucei, however, a knockdown of CRK1 and CRK2 resulted only in an enrichment of cells in G1 phase without cessation of DNA synthesis or elongated/branched posterior ends. A triple knockdown of CRK1, CRK2 and CycE1/CYC2 in the bloodstream form resulted in 15% of the cells arrested in G1 phase, but no cells had an abnormal posterior morphology. The double and triple knockdown bloodstream-form cells were differentiated in vitro into the procyclic form, and the latter thus generated bore the typical morphology of a procyclic form without an extended/branched posterior end, albeit arrested in the G1 phase as the bloodstream-form precursor. There is thus a major distinction in the mechanisms regulating G1-S transition and posterior morphogenesis between the two life stages of T. brucei.


Photo-driven molecular devices.
In this critical review, we discuss switching of the light-powered bistable rotaxanes and catenanes and highlight the practical applications of some of these systems. Photoactive molecular and supramolecular machines are comprised of two parts-1) a switching element, based on noncovalent interactions within the recognition units, which is responsible for executing mechanical movement, and 2) a light-harvesting unit which utilizes light to control the competitive interactions between the recognition sites. We also survey another class of molecular devices, namely molecular rotary motors--i.e., those that behave like their macroscopic counterparts--in which photochemically and thermally induced mechanical movement relies on isomerizations of a pivotal C=C bond, leading to a rotation of the top propeller part with respect to the stationary bottom part of the helical shaped chiral molecule. (146 references.).


Upper respiratory tract complications of gastroesophageal reflux in adult and pediatric-age patients.
Upper airway complications of gastroesophageal reflux occur much less frequently than those abroad to the upper esophageal sphincter; however, laryngitis, laryngeal and/or tracheal stenosis, globus syndrome, oropharyngeal dysphagia, otitis media, sinusitis, and rhinitis can all be associated with significant morbidity and occasional mortality in both adult and pediatric patients. Sudden infant death and apparent life-threatening events, both found only in pediatric patients, are even less frequently associated with gastroesophageal reflux. Today, excellent diagnostic methods are available, such as proximal 24-hour pH probe evaluations or scintigraphy, making proper diagnosis much easier than previously. Although today's medical and surgical methods do not affect the underlying pathophysiology, they are frequently very effective in controlling signs and symptoms, allowing the patients to return to resume their normal life-styles and livelihoods.


c-fos expression in the rat hypothalamic paraventricular nucleus induced by LiCl: descending projections to the dorsal vagal motor nucleus.
Anorexia inducing lithium chloride is believed to involve descending projections from hypothalamus to preganglionic autonomic output neurons. A multiple-labelling technique has presently been used to analyze the anatomical projections of lithium chloride sensitive neurons in the hypothalamus. Immunolabelling of c-fos was performed to stain neurons activated after LiCl administration, while neurons projecting toward vagal parasympathetic preganglionic levels were identified by injection of diamidino yellow in the dorsal motor nucleus of the vagus. Perikarya of descending neurons were mainly observed in the ventral and lateral areas of the paraventricular hypothalamic nucleus. In contrast, lithium chloride activated neurons were observed mainly in the magnocellular division of the paraventricular nucleus and supraoptic nucleus. Double-labelled neurons were not observed. These data provide evidence that lithium chloride sensitive neurons in the paraventricular nucleus are clearly different from those descending toward preganglionic vagal outflow neurons.


Histone deacetylases: revealing the molecular base of dimorphism in pathogenic fungi.
Fungi, as every living organism, interact with the external world and have to adapt to its fluctuations. For pathogenic fungi, such interaction involves adapting to the hostile environment of their host. Survival depends on the capacity of fungi to detect and respond to external stimuli, which is achieved through a tight and efficient genetic control. Chromatin modifications represent a well-known layer of regulation that controls gene expression in response to environmental signals. However, less is known about the chromatin modifications that are involved in fungal virulence and the specific cues and signalling pathways that target chromatin modifications to specific genes. In a recently published study, our research group identified one such regulatory pathway. We demonstrated that the histone deacetylase (HDAC) Hos2 is involved in yeast-to-hyphal transition (dimorphism) and it is associated with the virulence of the maize pathogen Ustilago maydis, the causative agent of smut disease in corn. Hos2 activates mating-type genes by directly binding to their gene bodies. Furthermore, Hos2 acts downstream of the nutrient-sensing cyclic AMP-Protein Kinase A pathway. We also found that another HDAC, Clr3, contributes to this regulation, possibly in cooperation with Hos2. As a whole, our data suggest that there is a direct link between changes in the environment and acetylation of nucleosomes within certain genes. We propose that histone acetylation is critical to the proper timing and induction of transcription of the genes encoding factors that coordinate changes in morphology with pathogenesis.


Left sided flank pain due to Bochdalek hernia with intrathoracic kidney.
A 40 year old woman had undergone surgery as a newborn due to a left sided congenital Bochdalek hernia with the ventricle, spleen, left kidney and adrenal gland located intrathoracically. After three pregnancies, she developed left sided flank pain and dyspnea. A CT scan showed a diaphragmatic hernia with a malrotated intrathoracic placed left kidney with minimal hydronephrosis. The spleen was located caudally in the left iliac fossa; there were no other abnormalities. The patient underwent a thoracotomy with a small resection of the diaphragm in order to replace the kidney in the abdominal cavity and closure of the diaphragmatic defect with a Gore-Tex patch.


[Vascular Vibration Injury and Paget-Shroetter Syndrome].
Paget-Schroetter syndrome is a relatively uncommon condition related to primary thrombosis of the axillary/subclavian vein at the costoclavicular junction. Vibration injury is an unusual cause of this syndrome. We report on a 28-year-old man who presented with acute onset left arm swelling after whole-day work with a pneumatic drill. Duplex ultrasound confirmed the presence of a thrombus in his left axillary and subclavian vein, which was treated with low molecular weight heparin, eventually switched to oral anticoagulation.


Identification, expression, and molecular evolution of microRNAs in the "living fossil" Triops cancriformis (tadpole shrimp).
MicroRNAs have been identified and analyzed in various model species, but an investigation of miRNAs in nonmodel species is required for a more complete understanding of miRNA evolution. In this study, we investigated the miRNAs of the nonmodel species Triops cancriformis (tadpole shrimp), a "living fossil," whose morphological form has not changed in almost 200 million years. Dramatic ontogenetic changes occur during its development. To clarify the evolution of miRNAs, we comparatively analyzed its miRNAs and the components of its RNAi machinery. We used deep sequencing to analyze small RNA libraries from the six different developmental stages of T. cancriformis (egg, first-fourth instars, and adult), and also analyzed its genomic DNA with deep sequencing. We identified 180 miRNAs (87 conserved miRNAs and 93 novel candidate miRNAs), and deduced the components of its RNAi machinery: the DICER1, AGO1-3, PIWI, and AUB proteins. A comparative miRNA analysis of T. cancriformis and Drosophila melanogaster showed inconsistencies in the expression patterns of four conserved miRNAs. This suggests that although the miRNA sequences of the two species are very similar, their roles differ across the species. An miRNA conservation analysis revealed that most of the conserved T. cancriformis miRNAs share sequence similarities with those of arthropods, although T. cancriformis is called a "living fossil." However, we found that let-7 and DICER1 of T. cancriformis are more similar to those of the vertebrates than to those of the arthropods. These results suggest that miRNA systems of T. cancriformis have evolved in a unique fashion.


Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion.
It has been increasingly demonstrated that the tumor microenvironment plays an active role in neoplasia growth and metastasis. Through different pathways, tumor cells can efficiently recruit stromal, immune and endothelial cells by secreting stimulatory factors, chemokines and cytokines. In turn, these cells can alter the signaling properties of the microenvironment by releasing growth-promoting signals, metabolites and extracellular matrix components to sustain high proliferation and metastatic competence. In this context, we identify that the complement component C1q, highly expressed locally by a range of human malignant tumors, upon interacting with the extracellular matrix hyaluronic acid, strongly affects the behavior of primary cells isolated from human tumor specimens. Here, we describe a method to test how C1q bound to hyaluronic acid (HA) impacts tumor cell adhesion, underlying the fact that the biological properties of key components of the extracellular matrix (in this case HA) can be shaped by bioactive signals toward tumor progression.


Effect of Religious Cognitive Behavioral Therapy on Religious Obsessive-compulsive Disorder (3 and 6 months Follow-up).
Obsessive-compulsive disorder (OCD) is a chronic disorder that strongly affects one's life and social, emotional, and occupational functioning. Due to the effect of religious beliefs on phenomenology of OCD, in this paper, we assess the effectiveness of religious cognitive behavioral therapy (CBT) within 3 and 6 months follow-up. This study is a clinical trial with follow-ups which last 2 months consisting eight sessions of 1.5 h of religious CBT. The research is conducted in a group of 40, with pre- and post-test after 3 and 6 months. Used Yale-Brown OCD symptom scale, before, the end, after 3 months and after 6 months of intervention. Treatment is carried out by a psychiatrist and a clergyman through religious CBT. The trial is held in OCD clinic affiliated with Noor Hospital. Results are analyzed by ANOVA repeated measure with SPSS18. The results showed a considerable decrease in OCD symptoms which remained almost persistent after 3 and 6 months (F = 3/54. P = 0/024). It also shows that religious CBT can leave substantial effect on OCD symptoms; permanency of this intervention after 3 and 6 months is noticeable (P < 0/001). In Conclusion this therapy could be helpful for OCD patients with religious content. RCBT have a positive effect on people with religious obsessive -compulsive.


Effect of pinealectomy on the circadian clock of the chick retina under different monochromatic lights.
The avian circadian rhythm pacemaker is composed of the retina, pineal gland and suprachiasmatic nucleus. As an intact input-pacemaker-output system, each of these structures is linked within a neuroendocrine loop to influence downstream processes and peripheral oscillations. While our previous study found that monochromatic light affected the circadian rhythms of clock genes in the chick retina, the effect of the pineal gland on the response of the retinal circadian clock under monochromatic light still remains unclear. In this study, a total of 144 chicks, including sham-operated and pinealectomized groups, were exposed to white, red, green or blue light. After 2 weeks of light illumination, the circadian expression of six core clock genes (cClock, cBmal1, cCry1, cCry2, cPer2 and cPer3), melanopsin (cOpn4-1, cOpn4-2), Arylalkylamine N-acetyltransferase (cAanat) and melatonin was examined in the retina. The cBmal1, cCry1, cPer2, cPer3, cOpn4-1, cOpn4-2 and cAanat genes as well as melatonin had circadian rhythmic expression in both the sham-operated and pinealectomized groups under different monochromatic lights, while cClock and cCry2 had arrhythmic 24 h profiles in all of the light-treated groups. After pinealectomy, the rhythmicity of the clock genes, melanopsins, cAanat and melatonin in the chick retina did not change, especially the mesors, amplitudes and phases of cBmal1, cOpn4-1, cOpn4-2, cAanat and melatonin. Compared to the white light group, however, green light increased the mRNA expression of the positive-regulating clock genes cBmal1, cAanat, cOpn4-1 and cOpn4-2 as well as the melatonin content in pinealectomized chicks, whereas red light decreased their expression. These results suggest that the chick retina is a relatively independent circadian oscillator from the pineal gland, whose circadian rhythmicity (including photoreception, molecular clock and melatonin output) is not altered after pinealectomization. Moreover, green light increases ocular cAanat expression and melatonin synthesis by accelerating the expression of melanopsin and positive-regulating clock genes cBmal1 and cClock.


Development of strategies for genetic manipulation and fine-tuning of a chloroplast retrograde signal 3'-phosphoadenosine 5'-phosphate.
Homeostasis of metabolism and regulation of stress-signaling pathways are important for plant growth. The metabolite 3'-phosphoadenosine-5'-phosphate (PAP) plays dual roles as a chloroplast retrograde signal during drought and high light stress, as well as a toxic by-product of secondary sulfur metabolism, and thus, its levels are regulated by the chloroplastic phosphatase, SAL1. Constitutive PAP accumulation in sal1 mutants improves drought tolerance but can impair growth and alter rosette morphology. Therefore, it is of interest to derive strategies to enable controlled and targeted PAP manipulation that could enhance drought tolerance while minimizing the negative effects on plant growth. We systematically tested the potential and efficiency of multiple established transgenic manipulation tools in altering PAP levels in Arabidopsis. Dexamethasone (dex)-inducible silencing of SAL1 via hpRNAi [pOpOff:SAL1hpRNAi] yielded reduction in SAL1 transcript and protein levels, yet failed to significantly induce PAP accumulation. Surprisingly, this was not due to insufficient silencing of the inducible system, as constitutive silencing using a strong promoter to drive hpRNAi and amiRNA targeting the SAL1 transcript also failed to increase PAP content or induce a sal1-like plant morphology despite significantly reducing the SAL1 transcript levels. In contrast, using dex-inducible expression of SAL1 cDNA to complement an Arabidopsis sal1 mutant successfully modulated PAP levels and restored rosette growth in a dosage-dependent manner. Results from this inducible complementation system indicate that plants with intermediate PAP levels could have improved rosette growth without compromising its drought tolerance. Additionally, preliminary evidence suggests that SAL1 cDNA driven by promoters of genes expressed specifically during early developmental stages such as ABA-Insensitive 3 (ABI3) could be another potential strategy for studying and optimizing PAP levels and drought tolerance while alleviating the negative impact of PAP on plant growth in sal1. Thus, we have identified ways that can allow future dissection into multiple aspects of stress and developmental regulation mediated by this chloroplast signal.


Heart failure and chronic obstructive pulmonary disease: Two for tea or tea for two?
A combination of chronic obstructive pulmonary disease (COPD) and heart failure (HF) is common yet it is inadequately and rarely recognized. Because of the similar clinical manifestations, comorbidity is frequently not considered and appropriate diagnostic tests are not performed. It is very important that a combination of COPD and HF is recognized as these patients have a worse prognosis than patients with an individual disease. When present, COPD should not prevent the use of life-saving therapy in patients with HF, particularly β-blockers. Despite clear evidence of the safety and tolerability of cardioselective β-blockers in COPD patients, these drugs remain grossly underprescribed and underdosed. Routine spirometry and echocardiography in HF and COPD patients, respectively, is therefore warranted to improve current clinical practice.


Facial appearance in glycogen storage disease type III.
Amylo-1,6-glucosidase deficiency (glycogen storage disease type III) is associated with hypoglycaemia, hepatomegaly, raised transaminases and in most cases skeletal myopathy and cardiomyopathy. The disorder has not been considered to cause dysmorphism. We report consistent facial features in seven patients with GSD type III consisting of midface hypoplasia with a depressed nasal bridge and a broad upturned nasal tip, indistinct philtral pillars, and bow-shaped lips with a thin vermillon border. Younger patients had in addition deepset eyes. Several children had clinical problems such as persistent otitis media or recurrent sinusitis. The underlying aetiology of these features is unknown but the similarity in all our patient suggests that there is a facial phenotype for this disorder.


Efficacy of ventricular rate stabilization by right ventricular pacing during atrial fibrillation.
To assess the effect of right ventricular pacing on rate regularity during exercise and daily life activities, 16 patients with sinoatrial disease and chronic atrial fibrillation (AF) were studied. Incremental ventricular pacing was commenced at 40 beats/min until > 95% of ventricular pacing were achieved during supine, sitting, and standing. Thirteen patients also underwent randomized paired submaximal exercise tests in either a fixed rate mode. (VVI) or a ventricular rate stabilization (VRS) mode in which the pacing rate was set manually at 10 beats/min above the average AF rate during the last minute of each exercise stage. The pacing interval for rate regularization was shortest during standing (692 +/- 26 ms) compared with either supine or sitting (757 +/- 30 and 705 +/- 26 ms, respectively, P < 0.05). During exercise VRS pacing significantly increased the maximum rate (119 +/- 5.2 vs 106 +/- 4.2 ms, P < 0.05), percent of ventricular pacing (85% +/- 5% vs 23% +/- 7%, P < 0.05), rate regularity index (5.8% +/- 1.6% vs 13.4% +/- 1.9%, P < 0.05), and maximum level of oxygen consumption (12.4 +/- 0.5 vs 11.3 +/- 0.5 mL/kg, P < 0.05) compared with VVI pacing. There was no change in oxygen pulse or difference in symptom scores in this acute study between the two pacing modes. It is concluded that right ventricular pacing may significantly improve rate regularity and cardiopulmonary performance in patients with chronic AF. This may be incorporated in a pacing device for rate regularization of AF using an algorithm that is rate adaptive to postural and exercise stresses.


Two polymorphs of cobalt(II) imidazolate polymers synthesized solvothermally by using one organic template N,N-dimethylacetamide.
Two structurally different polymorphs of cobalt(II) imidazolate frameworks are solvothermally synthesized by using N,N-dimethylacetamide as a template: The polymorph 6 (a = 9.797 (4) angstroms, b = 15.301(6) angstroms, c =14.902(6) angstroms, beta = 98.904(6) degrees, monoclinic, P21/n) shows structures of silicate CaAl2Si2O8 with CrB4 topology, while polymorph 7 (a = 15.173(4) angstroms, b = 15.173(4) angstroms, c = 19.089(5) angstroms, Pbca) shows CaGa2O4-related topological structures. In addition, the 7' (a = 15.9712(18) angstroms, b = 15.9253(19) angstroms, c = 18.475(2) angstroms, Pbca), a compound isostructural with 7, is synthesized by using cyclohexanol as a template. Thus, these cobalt(II) imidazolate polymers are reminiscent of the zeolite syntheses in that not only the same topological structure can be synthesized by using the different organic templates, but also different topological structures can be synthesized by using the same organic template.


Psychosocial risks in small enterprises: the mediating role of perceived working conditions in the relationship between enterprise size and workers' anxious or depressive episodes.
Purpose. The relationship between enterprise size and psychosocial working conditions has received little attention so far but some findings suggest that conditions are more favorable in small enterprises. This could have a positive impact on workers' mental health. The objective of this study was to test the mediating effect of perceived working conditions in the relationship between enterprise size and anxious or depressive episodes. Methods. Data from the 2010 SUMER - Surveillance Médicale des Expositions aux Risques professionnels (French periodical cross-sectional survey) were analyzed; N = 31,420 for the present study. Anxious or depressive episodes were measured with the hospital anxiety and depression scale and the perceived working conditions were psychological demand, decision latitude and social support as assessed with Karasek's job content questionnaire. The indirect effect was tested according to the method proposed by Preacher and Hayes. Results. In a multivariate logistic regression, the risk of anxious or depressive episodes was found to be lower in micro enterprises (2-9 employees). Formal tests pointed to a significant indirect effect of enterprise size on mental health through perceived working conditions, with a larger effect for psychological demand. Conclusion. This study highlights perceived working conditions as an explanation of the effects of enterprise size.


Coming soon to a screen near you.
As eLife starts to publish the accepted versions of certain Research Articles, we explain what happens once a manuscript has been accepted for publication.


Design and Application of a High-Throughput, High-Content Screening System for Natural Product Inhibitors of the Human Parasite Trichomonas vaginalis.
It is estimated that Trichomonas vaginalis affects an astonishing 3.9% of the world's population, and while many of those infected are asymptomatic, progression of the disease can lead to serious health problems. Currently, the nitroimidazoles constitute the only drug class approved to treat trichomoniasis in the United States, which makes the spread of drug resistance a realistic concern. We developed a new image-based, high-throughput, and high-content assay for testing natural products (purified compounds and extracts) for antitrichomonal activity. Applying this assay system to a library of fungal natural product extracts led to the identification of three general classes of natural product inhibitors that exhibited moderate to strong activities against T. vaginalis: anthraquinones, xanthone-anthraquinone heterodimers, and decalin-linked tetramic-acid-containing metabolites. The tetramate natural products emerged as the most promising candidate molecules with pyrrolocin A (51) exhibiting potent activity against the parasite (EC50 = 60 nM), yet this metabolite showed limited toxicity to mammalian cell lines (selectivity index values of 100 and 167 versus 3T3 fibroblast and Ect1 normal cervical cells, respectively). The imaging-based assay system is a powerful tool for the bioassay-guided purification of single-component antitrichomonal biomolecules from complex natural product mixtures.


3D analysis of eddy current loss in the permanent magnet coupling.
This paper first presents a 3D analytical model for analyzing the radial air-gap magnetic field between the inner and outer magnetic rotors of the permanent magnet couplings by using the Amperian current model. Based on the air-gap field analysis, the eddy current loss in the isolation cover is predicted according to the Maxwell's equations. A 3D finite element analysis model is constructed to analyze the magnetic field spatial distributions and vector eddy currents, and then the simulation results obtained are analyzed and compared with the analytical method. Finally, the current losses of two types of practical magnet couplings are measured in the experiment to compare with the theoretical results. It is concluded that the 3D analytical method of eddy current loss in the magnet coupling is viable and could be used for the eddy current loss prediction of magnet couplings.


Artificial intelligence fracture recognition on computed tomography: review of literature and recommendations.
The use of computed tomography (CT) in fractures is time consuming, challenging and suffers from poor inter-surgeon reliability. Convolutional neural networks (CNNs), a subset of artificial intelligence (AI), may overcome shortcomings and reduce clinical burdens to detect and classify fractures. The aim of this review was to summarize literature on CNNs for the detection and classification of fractures on CT scans, focusing on its accuracy and to evaluate the beneficial role in daily practice. Literature search was performed according to the PRISMA statement, and Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Google Scholar databases were searched. Studies were eligible when the use of AI for the detection of fractures on CT scans was described. Quality assessment was done with a modified version of the methodologic index for nonrandomized studies (MINORS), with a seven-item checklist. Performance of AI was defined as accuracy, F1-score and area under the curve (AUC). Of the 1140 identified studies, 17 were included. Accuracy ranged from 69 to 99%, the F1-score ranged from 0.35 to 0.94 and the AUC, ranging from 0.77 to 0.95. Based on ten studies, CNN showed a similar or improved diagnostic accuracy in addition to clinical evaluation only. CNNs are applicable for the detection and classification fractures on CT scans. This can improve automated and clinician-aided diagnostics. Further research should focus on the additional value of CNN used for CT scans in daily clinics.